Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Jun 10;12(6):534.
doi: 10.3390/pharmaceutics12060534.

Investigating the Potential of Transmucosal Delivery of Febuxostat from Oral Lyophilized Tablets Loaded with a Self-Nanoemulsifying Delivery System

Yasir A Al-Amodi  1 , Khaled M Hosny  1   2 , Waleed S Alharbi  1 , Martin K Safo  3 , Khalid M El-Say  1   4
Affiliations

Investigating the Potential of Transmucosal Delivery of Febuxostat from Oral Lyophilized Tablets Loaded with a Self-Nanoemulsifying Delivery System

Yasir A Al-Amodi et al. Pharmaceutics. .

Abstract

Gout is the most familiar inflammatory arthritis condition caused by the elevation of uric acid in the bloodstream. Febuxostat (FBX) is the latest drug approved by the United States Food and Drug Administration (US FDA) for the treatment of gout and hyperuricemia. FBX is characterized by low solubility resulting in poor gastrointestinal bioavailability. This study aimed at improving the oral bioavailability of FBX by its incorporation into self-nanoemulsifying delivery systems (SNEDS) with minimum globule size and maximum stability index. The SNEDS-incorporated FBX was loaded into a carrier substrate with a large surface area and lyophilized with other excipients to produce a fluffy, porous-like structure tablet for the transmucosal delivery of FBX. The solubility of FBX was studied in various oils, surfactants, and cosurfactants. Extreme vertices design was utilized to optimize FBX-SNEDS, and subsequently loaded into lyophilized tablets along with suitable excipients. The percentages of the main tablet excipients were optimized using a Box-Behnken design to develop self-nanoemulsifying lyophilized tablets (SNELTs) with minimum disintegration time and maximum drug release. The pharmacokinetics parameters of the optimized FBX-SNELTs were tested in healthy human volunteers in comparison with the marketed FBX tablets. The results revealed that the optimized FBX-SNELTs increased the maximum plasma concentration (Cmax) and decreased the time to reach Cmax (Tmax) with a large area under the curve (AUC) as a result of the enhanced relative oral bioavailability of 146.4%. The significant enhancement of FBX bioavailability is expected to lead to reduced side effects and frequency of administration during the treatment of gout.

Keywords: bioavailability; febuxostat; gout; lyophilized tablets; self-nanoemulsifying delivery system.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Solubility of FBX in different (a) oils, (b) surfactants, and (c) cosurfactants.
Figure 2
Figure 2
Pseudo-ternary phase diagrams of the selected nanoemulsion system (a), Two-dimensional (2D) contour plots of the estimated response surface for the effect of variables on FBX-SNEDS (b–d). The red area in figure (a) represents the clear nanoemulsion region that was selected as a border of the mixture experimental design space.
Figure 3
Figure 3
Photomicrographs of the optimized FBX-SNEDS by TEM image.
Figure 4
Figure 4
Disintegration (a) and dissolution profiles (b, c, and d) of the prepared SNELTs.
Figure 5
Figure 5
Pareto chart (a) and response surface plots (b–d) showing the effect of the independent variables on the disintegration time (Y1).
Figure 6
Figure 6
Pareto chart (a) and response surface plots (b–d) showing the effect of the independent variables on cumulative FBX release (Y2).
Figure 7
Figure 7
Comparative release profiles (a) and plasma concentration–time curves (b) between the optimized FBX-SNELTs and marketed tablets.
See this image and copyright information in PMC

References

    1. Perez-Ruiz F., Dalbeth N., Bardin T. A Review of Uric Acid, Crystal Deposition Disease, and Gout. Adv. Ther. 2014;32:31–41. doi: 10.1007/s12325-014-0175-z. - DOI - PMC - PubMed
    1. Altan A., Shiozawa A., Bancroft T., Singh J.A. A real-world study of switching from allopurinol to febuxostat in a health plan database. J. Clin. Rheumatol. 2015;21:411–418. doi: 10.1097/RHU.0000000000000322. - DOI - PMC - PubMed
    1. Li S., Yang H., Guo Y., Wei F., Yang X., Li D., Li M., Xu W., Li W., Sun L., et al. Comparative efficacy and safety of urate-lowering therapy for the treatment of hyperuricemia: A systematic review and network meta-analysis. Sci. Rep. 2016;6:1–12. doi: 10.1038/srep33082. - DOI - PMC - PubMed
    1. Khanna D., Fitzgerald J.D., Khanna P.P., Bae S., Singh M.K., Neogi T., Pillinger M.H., Merill J., Lee S., Prakash S., et al. American college of rheumatology guidelines for management of gout. part 1: Systematic nonpharmacologic and pharmacologic therapeutic approaches to hyperuricemia. Arthritis Care Res. 2012;64:1431–1446. doi: 10.1002/acr.21772. - DOI - PMC - PubMed
    1. Bisht M., Bist S. Febuxostat: A novel agent for management of Hyperuricemia in gout. Indian J. Pharm. Sci. 2012;73:597. doi: 10.4103/0250-474X.100231. - DOI - PMC - PubMed

LinkOut - more resources